7-71420984-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_022479.3(GALNT17):c.841G>A(p.Asp281Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: GALNT17 NM_022479.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.60

Genes affected

GALNT17 (HGNC:16347): (polypeptide N-acetylgalactosaminyltransferase 17) This gene encodes an N-acetylgalactosaminyltransferase. This gene is located centromeric to the common deleted region in Williams-Beuren syndrome (WBS), a multisystem developmental disorder caused by the deletion of contiguous genes at 7q11.23. This protein may play a role in membrane trafficking. [provided by RefSeq, Jan 2013]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GALNT17	NM_022479.3	c.841G>A	p.Asp281Asn	missense_variant	5/11	ENST00000333538.10
GALNT17	XM_011516467.4	c.841G>A	p.Asp281Asn	missense_variant	5/10
GALNT17	XM_017012521.3	c.841G>A	p.Asp281Asn	missense_variant	5/7
GALNT17	XM_011516469.4	c.841G>A	p.Asp281Asn	missense_variant	5/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GALNT17	ENST00000333538.10	c.841G>A	p.Asp281Asn	missense_variant	5/11	1	NM_022479.3	P1
GALNT17	ENST00000467723.1	n.775G>A		non_coding_transcript_exon_variant	5/11	2
GALNT17	ENST00000498380.6	n.1243G>A		non_coding_transcript_exon_variant	5/11	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000130 AC: 19 AN: 1461880 Hom.: 0 Cov.: 34 AF XY: 0.0000124 AC XY: 9 AN XY: 727244

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000144

Gnomad4 OTH exome AF: 0.0000497

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 26, 2024

The c.841G>A (p.D281N) alteration is located in exon 5 (coding exon 5) of the WBSCR17 gene. This alteration results from a G to A substitution at nucleotide position 841, causing the aspartic acid (D) at amino acid position 281 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
Cadd	Uncertain	25
Dann	Uncertain	1.0
DEOGEN2	Benign	0.27	T;.
Eigen	Benign	0.16
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D;D
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.50	D;D
MetaSVM	Benign	-0.95	T
MutationTaster	Benign	1.0	D
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-3.6	D;.
REVEL	Benign	0.22
Sift	Benign	0.21	T;.
Sift4G	Benign	0.32	T;T
Polyphen		0.041	B;.
Vest4		0.77
MutPred		0.53		Loss of sheet (P = 0.0817);.;
MVP		0.72
MPC		1.4
ClinPred		0.98	D
GERP RS		5.5
Varity_R		0.45
gMVP		0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-70885970;